Strana 86 VOJNOSANITETSKI PREGLED Vojnosanit Pregl 2013; 70(1): 86–89.
Correspondence to: Živko Perišiý, University Clinic for Obstetrics and Gynecology „Narodni front“, Kraljice Natalije 62, 11000 Bel-grade, Serbia. Phones: +381 63 21 66 77; +381 65 221 66 77. E-mail: zivkoperisic@gmail.com
I N F O C U S UDC: 618.146-006
DOI: 10.2298/VSP1301086P
Cervical cancer screening in Serbia
Skrining karcinoma grli
ü
a materice u Srbiji
Živko Perišiü*†, Vesna Plešinac-Karapandžiü‡, Milica Džiniü† , Milena Zamuroviü†, Nataša Perišiü†
*Faculty of Medicine, University of Belgrade, Serbia; †University Clinic of Gynecology and Obstetrics “Narodni front”, Belgrade, Serbia; ‡Institute of Oncology and Radiology
of Serbia, Belgrade, Serbia
Key words:
uterine cervical neoplasms; mass screening; diagnosis; cytological techniques; incidence.
Kljuÿne reÿi:
grliý materice, neoplazme; masovno ispitivanje; dijagnoza; citološke tehnike; incidenca.
Introduction
The article focuses on the beginning of cervical cancer screening in Serbia. The opportunistic screening was intro-duced in a regular gynecological practice in the early sixties and preventive gynecological examination has been per-formed since then on a yearly basis. The proportion of population screened was unknown, and the standards for quality assurance and control were not available. The na-tional program for such screening was established in 2011 encouraging women between 25 and 69 years to undergo a preventive gynecological examination together with Pap smear once in a 3-year period 1.
Based on the experience of countries with effectively organized screening programs, a decision was made in 2006 by the Minister of Health to nominate a group of experts to prepare a proposal for organized cervical cancer screening program after testing the methodology in a pilot study in the District of Braniþevo.
The specific objectives were to evaluate the reduction of the incidence and mortality from cervical cancer in the Province by means of an organized low-intensity cervical cytology program, as well as to demonstrate the different as-pects of program implementation as a potential model for nationwide implementation.
Screening activities were integrated in the existing health care system. Organized screening for women in the target population (aged 25–69 years) were planned to be free of charge. Sample taking was done by the gynecolo-gists and primary health care personnel in the local health care centers. Sample quality was under continuous control by the cytology laboratories. Confirmation and treatment were integrated into the normal health care routines. The
screening results of the program, including the histologi-cally confirmed diagnosis, were registered at the National Cancer Institute 1.
The impact of the screening program was assessed indi-rectly by comparing trends in invasive cervical cancer, changes in coverage, and changes in the interval between Pap smears.
Overview of the cervical cancer screening in Serbia during the years before
According to the data of the Register of Central Serbia for the Malignant Tumors 1,400 new cases of cervical can-cer are discovered on the territory of Serbia every year. Considering its frequency, this is the second frequent can-cer in women in Serbia, after breast cancan-cer. The standard-ized incidence rate of cervical cancer in the Central Serbia in 2002 was 27.2 in 100,000 women, which was the highest incidence rate in Europe. Similar, high rates were also re-corded in Romania, Albania and Bosnia and Herzegovina. According to the Institute of Statistics of the Republic of Serbia for the year 2002, a total of 452 women died be-cause of cervical cancer. The standardized mortality rate was 7.2 in 100,000 which was lower than in the mentioned countries of the region 2.
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Age distribution of patients with cervical cancer in Serbia
The risk for occurrence of cervical cancer increases with the age. The highest number of patients is between 45 and 54 years of age. However, the illness may, although very rare, occur even much earlier, e.g. even before 20 years of age. Age distribution of cervical cancer patients in Central Serbia in 2002 3 is shown in Table 1.
According to the available data, less than one third of the cases of cervical cancer ɚrɟ discovered in an early inva-sive phase in which only operative treatment can be success-fully applied. Most of patients are in later stages, when it is only possible to conduct radiotherapy, which results in longer treatment, different complications and significantly increased treatment expenses.
New cervical cancer screening program in Serbia
On July 3 2006 the Ministry of Health of the Republic of Serbia appointed the Expert Commission for the preven-tion of cervical cancer primarily aimed at developing a Na-tional Program for Prevention of Cervical Cancer.
Regarding the importance of the problem as well as the fact that in Serbia one woman dies per day due to cervical cancer, respecting the recommendations of WHO, and ana-lyzing screening programs of other countries and using the experiences from the Pilot Program from the District of Braniþevo, the Commission made the Program to enable the beginning of screening of cervical cancer in our country. This Program was adopted by the Government of the Re-public of Serbia issued in Official Gazette No 54 from 23 May 2008 1.
Serbia has enough gynecologists and other medical personnel to conduct screening. A partial change in organi-zation was expected to be achieved by introducing organ-ized screening. This primarily refers to education of cy-toscreeners and to organization of laboratory service for cytology.
On the territory of Serbia, screening of cervical cancer is conducted through an organized decentralized program.
The target group for cervical cancer screening
The decision on target group for cervical cancer screen-ing, as well as on interval between check-ups is most usually made on the national level considering the presence of cervical cancer, frequency of human papilloma virus (HPV) infections and available infrastructure means. The World Health
Organi-zation (WHO) recommends that the new screening programs should include women starting from 30 years of age. Women between 25 and 29 should be included only in the case when women of 30 + have been screened. Screening should not in-clude women under 25 years of age. In addition, screening in women older than 65 can be stopped, if they have two con-secutive negative findings 4.
According to data from the Central Serbia the frequency rate of cervical cancer is higher in all age groups in women between 35 and 74 years of age (Table 1). Because of this, es-tablishing the upper age limit, even over 65 years, would en-able the revealing of prevalent cases of cervical cancer. Mov-ing the lower limit of target group toward younger age groups, even despite the small risk for cervical cancer occurence, would enable revealing precancerous lesions.
The screening program included women between 25 and 69 years of age. The target group was identified with the help of election lists or data base of personal identification numbers and list of insured persons of the Republic of Serbia Bureau for Health Insurance. The call for testing was sent to all women from the target group.
Testing included cytological examination of cervical smear (Papanicolau test) observing the professional-methodological instructions. Screening was performed in every third year. Taking cervical smears was done by the Service for the Protection of Women’s Health in the Primary Health Care Center.
Cytological examination of cervical smear (Papanicolau test) underwent in cytological laboratory in the Primary Health Care Center and only for that Primary Health Care
Table 1 Age distribution of cervical cancer patients in Central Serbia in 2002 3
Patients Patient's age
(years)
n %
Age specific rate of cer-vical cancer per 100,000
patients
0–14 0 0.0 0.0
15–19 1 0.1 0.6
20–24 1 0.1 0.6
25–29 23 2.3 12.4
30–34 40 4.0 22.7
35–39 75 7.5 42.9
40–44 108 10.8 56.7
45–49 162 16.1 75.3
50–54 173 17.2 77.9
55–59 105 10.5 66.3
60–64 89 8.9 55.4
65–69 93 9.3 52.2
70–74 77 7.7 46.5
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Center, or in Primary Health Care Center which is responsi-ble for a whole district 1.
Reading the results of tests as well as determining the dynamic and content of further monitoring and referring to the other diagnostics was done by the Service for the Protec-tion of Women’s Health in the Primary Health Care Center. The results were read by the gynecologists who initially took smears for cytological diagnostics or the selected gynecolo-gists in the Primary Health Care Center.
In case of negative result, a patient was given a time recommendation for the next control examination and this was evidenced in the suitable Data Base of organized screening of cervical cancer. A patient stayed in a regular screening program and was called for the next check-up 3.
A positive result was reported by the doctor so that a patient understood the significance of further diagnostics. In case of inflammatory reversible changes, the patients were treated in the facilities of primary level and cytological test control was scheduled not earlie then 6 weeks after the treatment.
All the other histopathological findings required further procedure in accordance with the protocol for monitoring after receiving results from cytological examination. If a smear was unsatisfactory for cytological analysis, a patient was called again for the control examination in 6–8 weeks.
Referring the patients to the further diagnostics
A patient was referred to further diagnostics in a re-gional health facility of secondary level. With histopatho-logical finding the patient returned to the chosen doctor who, depending on the kind of a diagnosed change acted in accor-dance with the recommendations of the protocol for moni-toring women after receiving results from histopathological finding. In order to fulfill the whole value of the procedure it necessary to clearly define all the competences of various
levels of health care, as well as communication channels taking special care that the procedure be easy, acceptable and understandable for patients with the minimum of stress. It is extremely important to ensure adequate communication with patients at every level. This means explaining all possibilities of the treatment and its results, and getting an acceptance of further treatment, giving a patient an opportunity to freely ask questions in every phase of the treatment.
Women with low-grade lesions are submitted to routine follow-up smears. High-grade preinvasive disease was fur-ther evaluated by repeating Pap smear, conization or biopsy and subsequent treatment through surgical removal or abla-tion. This organized low-intensity cervical cytology pro-gramme showed a considerable increase in cervical intra-epithelial neoplasia (CIN) II–III cases and should reduce in-cidence of and mortality from cervical cancer in the future. Screening with the Papanicolaou smear plus adequate fol-low-up diagnosis and therapy can achieve major reductions in both incidence and mortality rates.
Uterine cervical cancer was one of the leading cancer among women in Serbia with age-standardized incidence rates of 23–27 per 100,000 in 2002 2. Cervical cancer inci-dence rate in Europe is shown in Figure 1.
Uterine cancer cervix is the second most common can-cer in females in the world with about half a million new
pa-tients per year 4. Cervical cancer is an important public health problem among adult women in developing coun-tries 5. Since the introduction by Papanicolaou of cervical smear screening, the incidence of cervical cancer has de-clined in many developed countries 2, 6. A decrease in the in-cidence of and the mortality from cervical cancer is mainly due to the organized mass screening using Pap smear pro-grams. To organize an effective screening program in devel-oping countries it should find adequate financial resources, develop the infrastructure, train the needed manpower, and
1.8 3.5 2.3 5.0 4.5 7.6 6.7 4.7 5.5 7.8 6.1 8.0 8.0 13.0 12.6
4.3 Finland
7.2 Ireland
7.3 Netherlands
13.3 Croatia
13.5 Portugal
13.9 FYR
Macedonia 15.7 Hungary
16.1 Slovenia
16.2 Czech
Republick 18.4 Poland
18.5 Slovakia
18.7 Bulgaria
21.3 Bosnia &
Herz.
23.9 Romania
27.3 C. Serbia
Standardised rate per 100 000 women, Globocan 2002
MT
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elaborate surveillance mechanisms for screening, investigat-ing, treatinvestigat-ing, and following up the targeted women. The findings from the large body of research on various screen-ing approaches carried out in developscreen-ing countries and from the available managerial guidelines should be taken into ac-count when reorganizing existing programmes and when considering new screening initiatives 7.
Cytological screening has reduced the incidence of cervi-cal cancer in countries with organized screening, but in Europe in 1995 there were still an estimated 68,000 incident cases 5, 7, 8. Cytology has limited reproducibility, and both meta-analyses and pooled analyses of cross sectional studies have established that tests for HPV have higher sensitivity than cytology in de-tecting high grade CIN and that combined HPV and cytology testing have high negative predictive values for CIN 9–11.
Cost-effectiveness modeling of screening strategies, however, depends greatly on reliable and generalisable esti-mates of the longitudinal, long term predictive values of
test-ing. A long-term negative predictive value is the main deter-minant of a safe screening interval to use, a key factor for the cost efficiency of a screening program. The long-term positive predictive value is an important measure of the extent of un-necessary procedures induced by screening, another major factor in evaluations of cost-efficiency. Several randomized controlled trials are currently being conducted to compare primary screening based on HPV detection with conventional cytology screening 12–17. Data from these trials indicate that HPV based screening results in detection of more high grade CIN lesions (a higher sensitivity) but a reduced specificity compared with cytology based screening 18–21.
Conclusion
The coordinated screening programme provides a low-cost, increases the coverage of the female population, and consequently reduces the rate of invasive cervical cancer.
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